染色体结合调节了由类域形成的凝聚物的相位行为和形态
Anushka Supakar1, Richoo B Davis2, Subhadip Biswas3
1Department of Biological Sciences, The State University of New York at Buffalo, Buffalo, NY 14260, USA.
Journal of molecular biology
|August 23, 2025
概括
转录因子形成核凝聚物. 染色体相互作用显著改变这些生物分子凝聚物,影响细胞核内的形状,动态和空间组织.
科学领域:
- 分子生物学
- 生物物理
- 细胞生物学
背景情况:
- 转录因子 (TF) 具有内在无序区域 (IDR) 并形成核生物分子凝聚物.
- TFs作为阻断共聚合物,IDRs调解蛋白相互作用和与染色体相互作用的DNA结合域 (DBDs).
- 试验室TF凝结物是球形和微米级的,与实体凝结物相反,这些凝结物是纳米级,非球形,并表现出不同的动态.
研究的目的:
- 研究TF-染色体相互作用如何调节活细胞中转录凝聚物的相位行为.
- 探索可调节的IDR-DBD架构在调节凝结物形态和动态中的作用.
- 阐明与体外模型相比,TF凝聚物的体内不同行为背后的机制.
主要方法:
- 工程融合蛋白结合SS18类域 (PLD) 与FOXA1DNA结合域 (DBD).
- 在细胞中过度表达融合蛋白,以观察凝聚物形成和局部化.
- 破坏DNA结合域-染色体相互作用,以评估它们对凝结物的影响.
- 使用粗粒模拟来模拟TF凝结物的行为和相互作用.
主要成果:
- SS18 PLD与FOXA1 DBD的融合导致凝结物重新定位为染色体,采用无球形状并表现出染色体湿.
- 破坏DBD-染色体结合,使凝聚物形态转向混合或球形状态.
- 染色素亲和度被确定为凝聚物粗化和空间组织的关键调节者.
- 模拟证实了PLD-PLD和DBD-DNA相互作用之间的平衡,这些相互作用决定了凝结物的结构和动态.
结论:
- TF- 染色体相互作用是体内转录凝聚物的关键决定因素.
- IDR介导的相互作用与DBD染色体结合之间的相互作用决定了凝结物的形态和动态.
- 工程TF构造提供了对核凝结物组织的调节的见解.
相关概念视频
02:41Chromatin Structure Regulates pre-mRNA Processing
7.2K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.2K
02:25Spreading of Chromatin Modifications
8.5K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.5K
02:05Duplication of Chromatin Structure
5.8K
The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
5.8K
02:54Nucleosome Remodeling
9.5K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
9.5K
02:38Heterochromatin
14.4K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
14.4K
01:45Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K